The current obstetrical practice at birth in the United States is that the umbilical cord of the very low birth weight (VLBW) infant is clamped immediately. When immediate cord clamping occurs, up to 25% of the fetal-placental blood volume may be left in the placenta acutely increasing vulnerability to hypovolemia. Hypovolemia can precipitate a cascade of physiologic events including poor tissue perfusion, ischemia, and initiation of the fetal/neonatal inflammatory response. Our previous Phase 1 randomized controlled trial of 72 VLBW infants born between 24 to 31 weeks gestation revealed fewer cases of intraventricular hemorrhage and late onset sepsis in infants who were randomized to delayed cord clamping (30 to 45 seconds) and lowered below the maternal introitus, compared to infants randomized to standard immediate cord clamping. We found a greater protective effect for male infants. Intraventricular hemorrhage (IVH) is a major cause of brain injury for preterm infants and is a predictor of poor neurodevelopment outcomes. Late onset sepsis (LOS) is also associated with morbidity and mortality in the NICU and later developmental delay. Of the approximately 57,000 infants born annually at less than 1500 grams, 10% develop cerebral palsy and 25 to 50% show later cognitive and behavioral deficits affecting school performance with higher rates found in males. We propose a larger trial with a sample of 212 randomized infants to validate our findings that delaying the cord clamping lowers the incidence of intraventricular hemorrhage and late onset sepsis, and to identify the mechanisms of effect through the study of biologic markers including measurement of cytokines (IL-6 and VEGF), circulating stem cells, and red cell volume. Enrolled women in preterm labor will be randomized at birth to the immediate cord clamping group or the delayed clamping group. Assessment of motor outcomes is planned at 7 months corrected age. This study will help to establish a scientific basis for the timing of cord clamping of VLBW infants. The innovation of this study is in the simplicity of delaying cord clamping for 30 to 45 seconds and lowering the VLBW infants at birth. This low-tech change in a clinical practice has the potential to reduce the risk of disease and disabililty and to improve the neonatal and early childhood outcomes for these most vulnerable preterm infants.Relevance. Intraventricular hemorrhage is a major cause of brain injury for preterm infants and late onset sepsis is also associated with morbidity and mortality in the NICU. Both are associated with later developmental delay. Of the approximately 57,000 infants born annually at less than 1500 grams, 10% develop cerebral palsy and 25 to 50% show later cognitive and behavioral deficits affecting school performance with higher rates found in males. If delaying cord clamping at the births of preterm infants lowers rates of intraventricular hemorrhage and late onset sepsis it may have a dramatic effect on the health and well being of these infants.